291 research outputs found
Improvements to the APBS biomolecular solvation software suite
The Adaptive Poisson-Boltzmann Solver (APBS) software was developed to solve
the equations of continuum electrostatics for large biomolecular assemblages
that has provided impact in the study of a broad range of chemical, biological,
and biomedical applications. APBS addresses three key technology challenges for
understanding solvation and electrostatics in biomedical applications: accurate
and efficient models for biomolecular solvation and electrostatics, robust and
scalable software for applying those theories to biomolecular systems, and
mechanisms for sharing and analyzing biomolecular electrostatics data in the
scientific community. To address new research applications and advancing
computational capabilities, we have continually updated APBS and its suite of
accompanying software since its release in 2001. In this manuscript, we discuss
the models and capabilities that have recently been implemented within the APBS
software package including: a Poisson-Boltzmann analytical and a
semi-analytical solver, an optimized boundary element solver, a geometry-based
geometric flow solvation model, a graph theory based algorithm for determining
p values, and an improved web-based visualization tool for viewing
electrostatics
Chloroquine and inhibition of Toll-like receptor 9 protect from sepsis-induced acute kidney injury
Mortality from sepsis has remained high despite recent advances in supportive and targeted therapies. Toll-like receptors (TLRs) sense bacterial products and stimulate pathogenic innate immune responses. Mice deficient in the common adapter protein MyD88, downstream from most TLRs, have reduced mortality and acute kidney injury (AKI) from polymicrobial sepsis. However, the identity of the TLR(s) responsible for the host response to polymicrobial sepsis is unknown. Here, we show that chloroquine, an inhibitor of endocytic TLRs (TLR3, 7, 8, 9), improves sepsis-induced mortality and acute kidney injury in a clinically relevant polymicrobial sepsis mouse model, even when administered 6h after the septic insult. Chloroquine administration attenuated the decline in renal function, splenic apoptosis, serum markers of damage to other organs, and prototypical serum pro- and anti-inflammatory cytokines TNF-alpha and IL-10. An oligodeoxynucleotide inhibitor (H154) of TLR9 and TLR9-deficient mice mirror the actions of chloroquine in all functional parameters that we tested. In addition, chloroquine decreased TLR9 protein abundance in spleen, further suggesting that TLR9 signaling may be a major target for the protective actions of chloroquine. Our findings indicate that chloroquine improves survival by inhibiting multiple pathways leading to polymicrobial sepsis, and that chloroquine and TLR9 inhibitors represent viable broad-spectrum and targeted therapeutic strategies, respectively, that are promising candidates for further clinical development
Statistical methods for building better biomarkers of chronic kidney disease
Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/149268/1/sim8091.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/149268/2/sim8091_am.pd
Research Needs for Effective Transition in Lifelong Care of Congenital Genitourinary Conditions: A Workshop Sponsored by the National Institute of Diabetes and Digestive and Kidney Diseases
Over the last 5 decades, health-care advances have yielded quantum improvements in the life expectancy of individuals with congenital genitourinary conditions (CGCs), leading to a crisis of care. Many individuals with CGC enter adulthood unprepared to manage their condition. Pediatric CGC specialists lack training to manage adulthood-related health-care issues, whereas adult genitourinary specialists lack training within the context of CGCs. To address these challenges, the National Institutes of Diabetes and Digestive and Kidney Diseases convened individuals with CGCs and experts from a variety of fields to identify research needs to improve transitional urology care. This paper outlines identified research needs
The effects of frequent nocturnal home hemodialysis: the Frequent Hemodialysis Network Nocturnal Trial
Prior small studies have shown multiple benefits of frequent nocturnal hemodialysis compared to conventional three times per week treatments. To study this further, we randomized 87 patients to three times per week conventional hemodialysis or to nocturnal hemodialysis six times per week, all with single-use high-flux dialyzers. The 45 patients in the frequent nocturnal arm had a 1.82-fold higher mean weekly stdKt/Vurea, a 1.74-fold higher average number of treatments per week, and a 2.45-fold higher average weekly treatment time than the 42 patients in the conventional arm. We did not find a significant effect of nocturnal hemodialysis for either of the two coprimary outcomes (death or left ventricular mass (measured by MRI) with a hazard ratio of 0.68, or of death or RAND Physical Health Composite with a hazard ratio of 0.91). Possible explanations for the left ventricular mass result include limited sample size and patient characteristics. Secondary outcomes included cognitive performance, self-reported depression, laboratory markers of nutrition, mineral metabolism and anemia, blood pressure and rates of hospitalization, and vascular access interventions. Patients in the nocturnal arm had improved control of hyperphosphatemia and hypertension, but no significant benefit among the other main secondary outcomes. There was a trend for increased vascular access events in the nocturnal arm. Thus, we were unable to demonstrate a definitive benefit of more frequent nocturnal hemodialysis for either coprimary outcome
Investigating Sub-Spine Actin Dynamics in Rat Hippocampal Neurons with Super-Resolution Optical Imaging
Morphological changes in dendritic spines represent an important mechanism for synaptic plasticity which is postulated to underlie the vital cognitive phenomena of learning and memory. These morphological changes are driven by the dynamic actin cytoskeleton that is present in dendritic spines. The study of actin dynamics in these spines traditionally has been hindered by the small size of the spine. In this study, we utilize a photo-activation localization microscopy (PALM)–based single-molecule tracking technique to analyze F-actin movements with ∼30-nm resolution in cultured hippocampal neurons. We were able to observe the kinematic (physical motion of actin filaments, i.e., retrograde flow) and kinetic (F-actin turn-over) dynamics of F-actin at the single-filament level in dendritic spines. We found that F-actin in dendritic spines exhibits highly heterogeneous kinematic dynamics at the individual filament level, with simultaneous actin flows in both retrograde and anterograde directions. At the ensemble level, movements of filaments integrate into a net retrograde flow of ∼138 nm/min. These results suggest a weakly polarized F-actin network that consists of mostly short filaments in dendritic spines
Azimuthal anisotropy in Au+Au collisions at sqrtsNN = 200 GeV
The results from the STAR Collaboration on directed flow (v_1), elliptic flow
(v_2), and the fourth harmonic (v_4) in the anisotropic azimuthal distribution
of particles from Au+Au collisions at sqrtsNN = 200 GeV are summarized and
compared with results from other experiments and theoretical models. Results
for identified particles are presented and fit with a Blast Wave model.
Different anisotropic flow analysis methods are compared and nonflow effects
are extracted from the data. For v_2, scaling with the number of constituent
quarks and parton coalescence is discussed. For v_4, scaling with v_2^2 and
quark coalescence is discussed.Comment: 26 pages. As accepted by Phys. Rev. C. Text rearranged, figures
modified, but data the same. However, in Fig. 35 the hydro calculations are
corrected in this version. The data tables are available at
http://www.star.bnl.gov/central/publications/ by searching for "flow" and
then this pape
Strangelet Search in AuAu Collisions at 200 GeV
We have searched for strangelets in a triggered sample of 61 million central
(top 4%) Au+Au collisions at \sNN = 200 GeV near beam rapidities at the STAR
detector. We have sensitivity to metastable strangelets with lifetimes of order
, in contrast to limits over ten times longer in AGS studies and
longer still at the SPS. Upper limits of a few 10^{-6} to 10^{-7} per central
Au+Au collision are set for strangelets with mass GeV/c^{2}.Comment: As publishe
Measurements of meson production in relativistic heavy-ion collisions at RHIC
We present results for the measurement of meson production via its
charged kaon decay channel in Au+Au collisions at
, 130, and 200 GeV, and in and +Au collisions
at GeV from the STAR experiment at the BNL Relativistic
Heavy Ion Collider (RHIC). The midrapidity () meson transverse
momentum () spectra in central Au+Au collisions are found to be well
described by a single exponential distribution. On the other hand, the
spectra from , +Au and peripheral Au+Au collisions show power-law tails
at intermediate and high and are described better by Levy
distributions. The constant yield ratio vs beam species, collision
centrality and colliding energy is in contradiction with expectations from
models having kaon coalescence as the dominant mechanism for production
at RHIC. The yield ratio as a function of is consistent
with a model based on the recombination of thermal quarks up to GeV/, but disagrees at higher transverse momenta. The measured nuclear
modification factor, , for the meson increases above unity at
intermediate , similar to that for pions and protons, while is
suppressed due to the energy loss effect in central Au+Au collisions. Number of
constituent quark scaling of both and for the meson
with respect to other hadrons in Au+Au collisions at =200 GeV
at intermediate is observed. These observations support quark
coalescence as being the dominant mechanism of hadronization in the
intermediate region at RHIC.Comment: 22 pages, 21 figures, 4 table
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